Improving the bioavailability of poorly water-soluble medicinal compounds has been an on-going challenge and remains of particular interest to many pharmaceutical researchers and pharmaceutical companies. In the present specification and claims a medicinal compound refers to a compound or formulation used to treat a medical condition and to a compound or formulation used as a precursor to create another medicinal compound.
An amorphous solid is characterized as a solid that does not have long-range order in its structure like a crystalline solid; it may have some short-range order on an atomic length scale because of chemical bonding. An amorphous solid has a disordered structure rather than a crystalline structure. Experimentally, the amorphicity of a solid can be characterized by an x-ray diffraction (XRD) pattern wherein no Bragg peaks are observed. To avoid any ambiguity in the present specification and claims, an amorphous solid is defined as a solid that does not exhibit Bragg peaks in its x-ray diffraction pattern when the x-ray exposure and detection parameters are sufficient to detect the Bragg peaks in a similar amount of the crystalline solid.
Because of its disordered structure, the enthalpy of an amorphous solid is higher than in a crystalline solid. The molecules are in an unstable energy state in the amorphous solid. This frustrated crystalline form causes an amorphous solid to have higher solubility than a crystalline solid does. According to a review paper, see Y. Kawabata et al.: International Journal of Pharmaceutics, Vol. 420, 1, (2011), the solubility difference between an amorphous solid and crystalline solid is typically from 1.1 to 1000 fold. Thus, use of an amorphous solid form of a medicinal compound is known as a way to improve its bioavailability because of the enhanced solubility due to its particular physical form.
Another strategy to improve bioavailability of a medicinal compound is to enlarge the relative surface area compared to the particle size by reducing the particle size of a drug using such as by a wet grinding process, a high pressure homogenization process, or a fluid bed spray-drying process. However, these methods have significant limitations. As exemplified in U.S. Pat. No. 7,597,278, in-liquid laser pulverization is an emerging technology to produce fine sized particles of medicinal compounds. A laser based approach offers many advantages over the conventional methods such as wet grinding, high pressure homogenization, or fluid bed spray-drying. A desirable advancement in such laser based processes would be to improve bioavailability, enhance solubility, and increase the yield of the particles.